Estrogen receptor inhibition enhances cold-induced adipocyte beiging and glucose tolerance
Kfir Lapid,1,2 Ajin Lim,1 Eric D Berglund,3,4 Yue Lu21Department of Developmental Biology; 2Division of Endocrinology, Department of Internal Medicine; 3Advanced Imaging Research Center; 4Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX, USABackground: ...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2019-08-01
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| Series: | Diabetes, Metabolic Syndrome and Obesity |
| Subjects: | |
| Online Access: | https://www.dovepress.com/estrogen-receptor-inhibition-enhances-cold-induced-adipocyte-beiging-a-peer-reviewed-article-DMSO |
| _version_ | 1797936188324052992 |
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| author | Lapid K Lim A Berglund ED Lu Y |
| author_facet | Lapid K Lim A Berglund ED Lu Y |
| author_sort | Lapid K |
| collection | DOAJ |
| description | Kfir Lapid,1,2 Ajin Lim,1 Eric D Berglund,3,4 Yue Lu21Department of Developmental Biology; 2Division of Endocrinology, Department of Internal Medicine; 3Advanced Imaging Research Center; 4Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX, USABackground: Low estrogen states, exemplified by postmenopausal women, are associated with increased adiposity and metabolic dysfunction. We recently reported a paradox, in which a conditional estrogen receptor-alpha (ERα) mutant mouse shows a hyper-metabolic phenotype with enhanced brown/beige cell formation (“browning/beiging”).Hypothesis: These observations led us to consider that although systemic deficiency of estrogen or ERα in mice results in obesity and glucose intolerance at room temperature, cold exposure might induce enhanced browning/beiging and improve glucose metabolism.Methods and results: Remarkably, studying cold-exposure in mouse models of inhibited estrogen signaling - ERαKO mice, ovariectomy, and treatment with the ERα antagonist Fulvestrant - supported this notion. ERα/estrogen-deficient mice demonstrated enhanced cold-induced beiging, reduced adiposity and improved glucose tolerance. Fulvestrant was also effective in diet-induced obesity settings. Mechanistically, ERα inhibition sensitized cell-autonomous beige cell differentiation and stimulation, including β3-adrenoreceptor-dependent adipocyte beiging.Conclusion: Taken together, our findings highlight a therapeutic potential for obese/diabetic postmenopausal patients; cold exposure is therefore predicted to metabolically benefit those patients.Keywords: adipose tissue, post-menopause, brown fat, obesity, diabetes |
| first_indexed | 2024-04-10T18:25:44Z |
| format | Article |
| id | doaj.art-9f0d650a27f3416cb2c4c286830004e9 |
| institution | Directory Open Access Journal |
| issn | 1178-7007 |
| language | English |
| last_indexed | 2024-04-10T18:25:44Z |
| publishDate | 2019-08-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Diabetes, Metabolic Syndrome and Obesity |
| spelling | doaj.art-9f0d650a27f3416cb2c4c286830004e92023-02-02T05:45:45ZengDove Medical PressDiabetes, Metabolic Syndrome and Obesity1178-70072019-08-01Volume 121419143647842Estrogen receptor inhibition enhances cold-induced adipocyte beiging and glucose toleranceLapid KLim ABerglund EDLu YKfir Lapid,1,2 Ajin Lim,1 Eric D Berglund,3,4 Yue Lu21Department of Developmental Biology; 2Division of Endocrinology, Department of Internal Medicine; 3Advanced Imaging Research Center; 4Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX, USABackground: Low estrogen states, exemplified by postmenopausal women, are associated with increased adiposity and metabolic dysfunction. We recently reported a paradox, in which a conditional estrogen receptor-alpha (ERα) mutant mouse shows a hyper-metabolic phenotype with enhanced brown/beige cell formation (“browning/beiging”).Hypothesis: These observations led us to consider that although systemic deficiency of estrogen or ERα in mice results in obesity and glucose intolerance at room temperature, cold exposure might induce enhanced browning/beiging and improve glucose metabolism.Methods and results: Remarkably, studying cold-exposure in mouse models of inhibited estrogen signaling - ERαKO mice, ovariectomy, and treatment with the ERα antagonist Fulvestrant - supported this notion. ERα/estrogen-deficient mice demonstrated enhanced cold-induced beiging, reduced adiposity and improved glucose tolerance. Fulvestrant was also effective in diet-induced obesity settings. Mechanistically, ERα inhibition sensitized cell-autonomous beige cell differentiation and stimulation, including β3-adrenoreceptor-dependent adipocyte beiging.Conclusion: Taken together, our findings highlight a therapeutic potential for obese/diabetic postmenopausal patients; cold exposure is therefore predicted to metabolically benefit those patients.Keywords: adipose tissue, post-menopause, brown fat, obesity, diabeteshttps://www.dovepress.com/estrogen-receptor-inhibition-enhances-cold-induced-adipocyte-beiging-a-peer-reviewed-article-DMSOAdipose tissuepost-menopausebrown fatobesitydiabetes |
| spellingShingle | Lapid K Lim A Berglund ED Lu Y Estrogen receptor inhibition enhances cold-induced adipocyte beiging and glucose tolerance Diabetes, Metabolic Syndrome and Obesity Adipose tissue post-menopause brown fat obesity diabetes |
| title | Estrogen receptor inhibition enhances cold-induced adipocyte beiging and glucose tolerance |
| title_full | Estrogen receptor inhibition enhances cold-induced adipocyte beiging and glucose tolerance |
| title_fullStr | Estrogen receptor inhibition enhances cold-induced adipocyte beiging and glucose tolerance |
| title_full_unstemmed | Estrogen receptor inhibition enhances cold-induced adipocyte beiging and glucose tolerance |
| title_short | Estrogen receptor inhibition enhances cold-induced adipocyte beiging and glucose tolerance |
| title_sort | estrogen receptor inhibition enhances cold induced adipocyte beiging and glucose tolerance |
| topic | Adipose tissue post-menopause brown fat obesity diabetes |
| url | https://www.dovepress.com/estrogen-receptor-inhibition-enhances-cold-induced-adipocyte-beiging-a-peer-reviewed-article-DMSO |
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